- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01566435
Induction Chemotherapy With ACF Followed by Chemoradiation Therapy for Adv. Head & Neck Cancer
September 9, 2020 updated by: Washington University School of Medicine
Phase II Trial of Nab-Paclitaxel, Cisplatin, and 5-FU (ACF) as Induction Therapy Followed by Definitive Concurrent Chemoradiation for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (HNSCC)
This phase II trial studies the safety and effectiveness of an induction chemotherapy (ACF) consisting of paclitaxel albumin-stabilized nanoparticle formulation (nab-paclitaxel), cisplatin and fluorouracil followed by chemoradiation therapy in treating patients with stage III-IV squamous cell cancer of the head and neck.
ACF may be an effective way to reduce or downgrade locally aggressive tumors, and improve the chance of eradication by chemoradiation.
Study Overview
Status
Completed
Conditions
Detailed Description
Compared to the standard induction regimen of TPF (docetaxel, cisplatin, and 5-FU), the ACCF (nab-paclitaxel, cisplatin, cetuximab, and 5-FU) regimen included two therapeutic changes: nab-paclitaxel was substituted for docetaxel and cetuximab was added.
The investigators propose to eliminate cetuximab from the ACCF regimen to isolate the treatment effects of nab-paclitaxel when given with cisplatin and 5-FU.
The primary objective of the ACF proposal is to determine the complete (CR) rate by clinical examination at the primary tumor site following two cycles of ACF.
An important secondary objective will be to compare the tumor response rates at the primary site following two cycles of ACF to our historical experience following two cycles of ACCF (protocol # ABX 218/HRPO# 08-0911).
In addition, the investigators will compare adverse events (AEs) between patients who receive ACF to the historical group given ACCF.
From these two comparisons, we aim to determine if either ACF or ACCF is superior based on a balance of efficacy (using the surrogate prognostic endpoint of CR rate at primary tumor site) and toxicity.
Study Type
Interventional
Enrollment (Actual)
30
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Patient must have selected stage III or IVa/b head and neck squamous cell carcinoma (HNSCC); all patients must have T2-T4 primary tumors; (patients with T1 tumors will be excluded); although most of these patients will have regional nodal disease, patients with no nodal disease will also be eligible
- Patient must have disease at the oropharynx, hypopharynx, larynx, or oral cavity sub-sites
- Patient must have measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 10 mm with CT scan
- Patient must be >= 18 years of age.
- Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Patient must have adequate bone marrow and organ function as defined below:
- Absolute neutrophil count (ANC) >= 1500/mcL
- Platelets > 100,000/mcL
- Hemoglobin > 9.0 g/dL
- Total bilirubin =< 1.5 mg/dL
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
- Alkaline phosphatase =< 2.5 x ULN
- Serum creatinine < 1.8 mg/dL
- Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 3 months after completing treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately
- Patient must be able to understand and willing to sign an Institutional Review Board (IRB)-approved written informed consent document
- Patient with uncontrolled diabetes or fasting blood glucose level of greater than 200 mg/dL will be eligible for enrollment but will not be evaluable for PET imaging
Exclusion Criteria:
- Patient must not have had prior chemotherapy, prior epidermal growth factor receptor (EGFR) targeted therapy, or prior radiation therapy for HNSCC
- Patient must not have disease at the nasopharyngeal, sinus, or other sub-site not specified in the inclusion criteria; patient must not have unknown primary squamous cell carcinoma of the head and neck
- Patient must not have a history of prior invasive malignancy diagnosed within 3 years prior to study enrollment other than local stage non-melanoma skin cancer
- Patient must not be receiving any other investigational agents
- Patient must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to any of the agents used in this study
- Patient must not be taking cimetidine or allopurinol. If currently taking either of these medications, patient must discontinue for one week before receiving treatment with nab-paclitaxel
- Patient must not have an uncontrolled intercurrent illness including, but not limited to, ongoing or active serious infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or serious psychiatric illness/social situations that would limit compliance with study requirements
- Patient must not be pregnant and/or breastfeeding; a negative serum or urine pregnancy test is required at screening for all female patients of childbearing potential
- Patient must not be known to be human immunodeficiency virus (HIV)-positive on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with the study agents; in addition, these patients are at increased risk of lethal infections when treated with marrow suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
- Patient must not have peripheral neuropathy > grade 1
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm 1-ACF Induction Therapy Followed by Chemoradiation Therapy
ACF Induction Therapy (Cycle 1 and Cycle 2 - each cycle is every 3 weeks)
If patient has complete or partial response, he/she will receive an additional ACF cycle (cycle 3). If patient has stable disease or progressive disease will not receive the third cycle of ACF. Definitive Therapy
|
Other Names:
Other Names:
Other Names:
Other Names:
Other Names:
ACF baseline, IMRT baseline, Day 7, Week 12, months 6 and 12
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With Complete Response (CR) by Clinical Exam at Primary Tumor Site
Time Frame: 6 weeks (2 cycles of therapy)
|
|
6 weeks (2 cycles of therapy)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With Partial Response (PR) at Primary Tumor Site
Time Frame: 6 weeks (2 cycles of therapy)
|
|
6 weeks (2 cycles of therapy)
|
Number of Participants Per Anatomic Tumor Response by CT Scan
Time Frame: 6 weeks (2 cycles of therapy)
|
|
6 weeks (2 cycles of therapy)
|
Metabolic Tumor Responses as Measured by FDG-PET/CT
Time Frame: 6 weeks (2 cycles of therapy)
|
|
6 weeks (2 cycles of therapy)
|
Overall Survival Rate
Time Frame: 2 years
|
-Overall survival rate is the percentage of participants who are alive at 2 years.
|
2 years
|
Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy
Time Frame: From start of treatment through 30 days after end of treatment
|
Assessed by NCI-CTCAE version 3
|
From start of treatment through 30 days after end of treatment
|
Changes in Secreted Protein Acidic and Rich in Cysteine (SPARC) Expression by Immunohistochemistry (IHC) in Primary Tumor Tissue
Time Frame: 6 weeks (2 cycles of therapy)
|
SPARC and Ki-67 expression will be assessed at this institution by IHC stains performed on clinically available tumor specimens (paraffin blocks).
The specimens will be collected retrospectively from prior biopsies (pre treatment and following 2 cycles of ACF) that will have consisted of a minimum of two needle cores (16-18 gauge) or two small incisional/excisional pieces of tumor.
These will have been placed in 2% buffered formalin and transported to the surgical pathology processing lab.
|
6 weeks (2 cycles of therapy)
|
Complete Response (CR) or Partial Response (PR) at Regional (Neck) Nodes as Measured by Clinical Exam
Time Frame: 6 weeks (2 cycles of therapy)
|
6 weeks (2 cycles of therapy)
|
|
Changes in Ki-67 Expression by Immunohistochemistry (IHC) in Primary Tumor Tissue
Time Frame: 6 weeks (2 cycles of therapy)
|
Ki-67 expression will be assessed at this institution by IHC stains performed on clinically available tumor specimens (paraffin blocks).
The specimens will be collected retrospectively from prior biopsies (pre treatment and following 2 cycles of ACF) that will have consisted of a minimum of two needle cores (16-18 gauge) or two small incisional/excisional pieces of tumor.
These will have been placed in 2% buffered formalin and transported to the surgical pathology processing lab.
|
6 weeks (2 cycles of therapy)
|
Disease-free Survival (DFS) Rate
Time Frame: 2 years
|
2 years
|
|
Progression-free Survival (PFS)
Time Frame: 2 years
|
-Progression: at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
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2 years
|
Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy - Head and Neck (FACT-H&N) Total Score
Time Frame: Through one year after completion of treatment
|
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Through one year after completion of treatment
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Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy - Head and Neck (FACT-H&N) FACT-G Total Score
Time Frame: Through end of chemoradiation
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|
Through end of chemoradiation
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Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy - Head and Neck (FACT-H&N) Trial Outcome Index (TOI)
Time Frame: Through end of chemoradiation
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Through end of chemoradiation
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Adkins D, Ley J, Oppelt P, Gay HA, Daly M, Paniello RC, Jackson R, Pipkorn P, Rich J, Zevallos J, Trinkaus K, Thorstad W. Impact on Health-Related Quality of Life of Induction Chemotherapy Compared With Concurrent Cisplatin and Radiation Therapy in Patients With Head and Neck Cancer. Clin Oncol (R Coll Radiol). 2019 Sep;31(9):e123-e131. doi: 10.1016/j.clon.2019.05.007. Epub 2019 May 28.
- Adkins D, Ley J, Oppelt P, Wildes TM, Gay HA, Daly M, Rich J, Paniello RC, Jackson R, Pipkorn P, Nussenbaum B, Trinkaus K, Thorstad W. nab-Paclitaxel-based induction chemotherapy with or without cetuximab for locally advanced head and neck squamous cell carcinoma. Oral Oncol. 2017 Sep;72:26-31. doi: 10.1016/j.oraloncology.2017.07.001. Epub 2017 Jul 8.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
August 9, 2012
Primary Completion (Actual)
October 31, 2013
Study Completion (Actual)
October 31, 2019
Study Registration Dates
First Submitted
March 27, 2012
First Submitted That Met QC Criteria
March 27, 2012
First Posted (Estimate)
March 29, 2012
Study Record Updates
Last Update Posted (Actual)
October 1, 2020
Last Update Submitted That Met QC Criteria
September 9, 2020
Last Verified
September 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Neoplasms by Site
- Head and Neck Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Antineoplastic Agents, Immunological
- Paclitaxel
- Antibodies
- Fluorouracil
- Albumin-Bound Paclitaxel
- Antibodies, Monoclonal
- Cetuximab
Other Study ID Numbers
- 201202113
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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